Methods and compositions for inhibiting enveloped viruses using high molecular weight hydrophobically modified alkali swellable emulsion polymers and surfactant

ABSTRACT

This invention relates to methods and compositions for inhibiting the transmission of enveloped viruses, which entails applying a composition containing a high molecular weight hydrophobically-modified polymer to an infectable or ingestible surface that may contain viruses and wherein said anti-viral composition comprises less than about 9% by weight of surfactant having an HLB greater than about 12.

FIELD OF THE INVENTION

The method of this invention relates to the use of high molecular weighthydrophobically modified polymers to inhibit the transmission of virusesknown as “enveloped” viruses. It also relates to compositions containingsaid high molecular weight hydrophobically modified polymers capable ofinhibiting transmission of said viruses.

BACKGROUND OF THE INVENTION

Infections due to enveloped viruses cause common diseases such as herpessimplex, HIV/AIDS, hepatitis B, influenza, chicken pox, shingles, smallpox, and respiratory infections. While the seriousness of these diseasescan range from moderately bothersome to life-threatening, theseinfections adversely affect the quality of life of its host and thepersonal, institutional and economic areas of our society. As a result,there have been substantial efforts to develop means to prevent viralinfection and its spread. These efforts are complicated by viraldiversity, the numerous means by which viruses are transmitted,including: direct contact, exchange of bodily fluids (e.g. saliva,sexual transmission, breast feeding), and aerosol transmission (e.g.coughing, sneezing, etc.) as well as the highly evolved measures bywhich viruses escape detection and/or eradication by their hosts. Therehave been numerous successes in the discovery and commercialization ofantiviral agents administered to those who have been infected with avirus. However, these treatments often require medical prescriptions,have unwanted side effects, only work on a narrow range of viraltypes/strains, and/or have limited efficacy. Topically deliveredantiviral treatments must also be non-irritating to the treated tissues,or risk increasing the risk of infection.

Therefore, cost effective and gentle agents with potent, broad-spectrumanti-viral activity which are capable of significantly reducing virustransmission would fill an unmet need in the antiviral armamentarium andhelp prevent the spread of viral infections, especially if mildproperties of such agents could permit and encourage widespread,frequent usage due to superior compatibility with skin, eyes and othermucosal membranes.

Viruses have high mutation and replication rates; these properties allowrapid evolution in response to external selective pressures (i.e. drug),often leading to treatment resistance and relapse. The concern ofresistance is especially salient when the antiviral compound targets aspecific epitope on the virion. Due to high levels of viral geneticdiversity, this narrow specificity also usually limits the range ofviruses sensitive to the compound. Alternatively, other topicalantiviral treatments, such as surfactants, target non-specific viralregions and are broadly effective at neutralizing diverse viruses,however, these are often irritating and toxic to human cells. Treatmentsthat irritate tissues may result in an increased infection rate;damaging cellular membranes increases their permeability to some typesof viral particles. Thus, a non-irritating yet highly effective meansfor eradicating viruses and significantly reducing their transmissionpotential would be highly desirable.

Most viruses (e.g., HIV and many animal viruses) have viral envelopes astheir outer layer at the stage of their life-cycle when they are betweenhost cells. Robertson et al. (March 1995). “Recombination in AIDSviruses.” Journal of Molecular Evolution. 40 (3): 249-59. Some envelopedviruses also have a protein layer called a capsid between the envelopeand their genome. Id. The envelopes are typically derived from portionsof the host cell membranes (phospholipids and proteins), but includesome viral glycoproteins. They may help viruses avoid the host immunesystem. Glycoproteins on the surface of the envelope serve to identifyand bind to receptor sites on the host's membrane. The viral envelopethen fuses with the host's membrane, allowing the capsid and viralgenome to enter and infect the host.

The cell from which the virus itself buds will often die or be weakenedand shed more viral particles for an extended period. The lipid bilayerenvelope of these viruses is relatively sensitive to desiccation, heat,and detergents; therefore these viruses are easier to sterilize thannon-enveloped viruses, have limited survival outside host environments,and typically transfer directly from host to host. Enveloped virusespossess great adaptability and can change in a short time in order toevade the immune system. Enveloped viruses can cause persistentinfections.

Classes of enveloped viruses that contain human pathogens include, e.g.,DNA viruses such as Herpesvirus, Poxviruses, Hepadnaviruses,Asfarviridae; RNA viruses such as Flavivirus, Alphavirus, Togavirus,Coronavirus, Hepatitis D, Orthomyxovirus, Paramyxovirus, Rhabdovirus,Bunyavirus, Filovirus; and Retroviruses such as HIV.

COVID-19

Coronaviruses (CoVs) are relatively large viruses containing asingle-stranded positive-sense RNA genome encapsulated within a membraneenvelope. The viral membrane is studded with glycoprotein spikes thatgive coronaviruses their crownlike appearance. (See FIG. 1, taken fromLiu et al., Research and Development on Therapeutic Agents and Vaccinesfor COVID-19 and Related Human Coronavirus Diseases, ACS Cent. Sci.2020, 6, 315-331). While coronaviruses infect both humans and animals,certain types of animals such as bats that host the largest variety ofcoronaviruses appear to be immune to coronavirus-induced illness. Thereare four classes of coronaviruses designated as alpha, beta, gamma, anddelta. The betacoronavirus class includes severe acute respiratorysyndrome (SARS) virus (SARS-CoV), Middle East respiratory syndrome(MERS) virus (MERS-CoV), and the COVID-19 causative agent SARS-CoV-2.Similar to SARS-CoV and MERS-CoV, SARS-CoV-2 attacks the lowerrespiratory system to cause viral pneumonia, but it may also affect thegastrointestinal system, heart, kidney, liver, and central nervoussystem leading to multiple organ failure. Current information indicatesthat SARSCoV-2 is more transmissible/contagious than SARS-CoV.

A number of studies have focused on elucidation of virus structure,virus transmission mechanisms/dynamics, as well as identification ofantiviral agents and accurate diagnostics for virus detection. Thesetrends reflect immense interest and desire from the scientificcommunity, including both academic and industrial organizations as wellas clinicians, to identify new methods to halt the progression of thisepidemic disease and to prevent infection and transmission in thefuture.

COVID-19 is caused by SARS-CoV-2, a new type of coronavirus in the samegenus as SARS-CoV and MERS-CoV. Viral proteins responsible forSARS-CoV-2 entry into host cells and replication are structurallysimilar to those associated with SARS-CoV. Thus, research anddevelopment on SARS and MERS may offer insights that would be beneficialto the development of therapeutic and preventive agents for COVID-19.

Arbidol, CAS No. 131707-23-8, which targets S protein/ACE2, is aninhibitor that may disrupt the binding of the viral envelope protein tohost cells and prevent entry of the virus to the target cell has enteredinto clinical trials for treatment of COVID-19. See Liu et al. above andFIG. 2 below, taken from Blaising et al., Arbidol as a broad-spectrumantiviral: An update, Antiviral Research, 107 (2014) 84-94. See alsoKadam et al., Structural basis of influenza virus fusion inhibition bythe antiviral drug Arbidol, PNAS Jan. 10, 2017 114 (2) 206-214.

The 2003 emergence of the severe acute respiratory disease coronavirus(SARS-CoV) demonstrated that CoVs are capable of causing outbreaks ofsevere infections in humans. A second severe CoV, Middle Eastrespiratory syndrome coronavirus (MERS-CoV), emerged in 2012 in SaudiArabia. More recently, COVID-19 identified in Wuhan, China, in December2019, has proven particularly detrimental.

Given that the polymers of the invention have shown activity againstenveloped viruses, it is expected that polymers of the invention mayalso show activity against COVID-19 by inhibiting entry of the virus ina host cell. See FIG. 3.

RetroVirox, San Diego, Calif., has developed cell-based assays that canbe used to evaluate experimental treatments against coronaviruses,including SARS-CoV-2. The Company provides testing with SARS-CoV-2pseudoviruses to evaluate entry inhibitors against the novel coronaviruscausative agent of COVID-19. The pseudovirus assay utilizes HIVpseudoviruses coated with the viral spike (S) protein of SARS-CoV-2(Wuhan isolate). The assay, which recapitulates the mode of entry of thenovel coronavirus, it can be used for, e.g., evaluate small-moleculeentry inhibitors targeting the S viral protein, the ACE-2 viralreceptor, or host proteases and other targets involved in SARS-CoV-2viral entry.

U.S. Pat. Nos. 7,803,403 and 8,025,902 to Johnson & Johnson ConsumerInc. disclose personal care compositions that contain a low molecularweight, non-cross linked, linear acrylic copolymer and at least onesurfactant; and a method of cleansing using said personal carecompositions.

U.S. Pat. Nos. 8,343,902 and 8,329,626 to Johnson & Johnson ConsumerInc. disclose a skin cleansing composition that comprises a lowmolecular weight, non-crosslinked, linear acrylic copolymer and anon-ethoxylated anionic surfactant.

U.S. Pat. No. 8,329,627 to Johnson & Johnson Consumer Inc. discloses aclear skin cleansing composition that comprises a low molecular weight,non-crosslinked, linear acrylic copolymer and a blend of at least twoamphoteric surfactants.

U.S. Pat. No. 8,293,845 to Lubrizol Corp. discloses a method forincreasing the critical micelle concentration of a surfactantcomposition comprising including a linear hydrophobically modified(meth)acrylic polymer in said composition.

U.S. Pat. No. 7,892,525 to Lubrizol Advanced Materials, Inc. disclosesantiperspirant compositions that comprise a cationic hydrophobicallymodified polymeric gelling agent and an acidic antiperspirant compound.

U.S. Pat. No. 9,068,148 to Lubrizol Advanced Materials, Inc. disclosesan acrylic polymer blend that comprises at least one crosslinked acryliccopolymer and at least one acrylic linear, non-crosslinked polymer; amethod for making the acrylic polymer blend; and method for thickeningan aqueous composition comprising the acrylic polymer blend.

U.S. Pat. No. 9,931,290 to Lubrizol Advanced Materials, Inc. discloses asurfactant composition that comprises a surfactant and a crosslinkedacrylic copolymer; and a personal care cleansing composition comprisingthe surfactant composition.

U.S. Pat. No. 10,517,806 to Ecolab USA Inc. claims a foamingantimicrobial dermal cleanser that comprises a cationic activeingredient; a cationic compatible surfactant; a foam boosting agent; afoam structure enhancing agent; a skin conditioning agent; and water.The reference claims a method of reducing bacterial, microbial,fungicidal, or viral population on a dermal tissue of a mammalcomprising contacting the dermal tissue with the foaming antimicrobialdermal cleanser. The reference also discloses that cationic activeingredients are antimicrobial agents useful in the present invention andthat the foam structure enhancing agent can be polyethyleneglycol. Thereference discloses the use of S. aureus and Escerichia coli as testmicrobial cultures to test microbial efficacy of the formulas therein.

U.S. Pat. No. 10,435,308 to Ecolab USA, Inc. claims a composition forimproving oil removal from an oil/aqueous phase solution by foamfractionation that comprises an associative thickener; a surfactantcomprising a sorbitan ester; and a viscoelastic surfactant, wherein theviscoelastic surfactant is a betaine, amine oxide, and/or ethoxylatedfatty amine. The reference discloses that the composition may be usedin, e.g., cleaning agents, cosmetics, pickles, aqueous pigment pastes,automotive finishes, industrial coatings, printing inks, lubricatinggreases, plaster paints and wall paints, textile coatings,pharmaceutical preparations, crop protection formulations, fillerdispersions, adhesives, detergents, wax dispersions, polishes,auxiliaries for tertiary mineral oil production etc.

U.S. Published Application No. 20160262999 to Ecolab USA, Inc. claims anantimicrobial dermal concentrate that comprises a cationic activeingredient; a foam boosting surfactant; a foam boosting copolymer; afoam stabilizing structure; and water. The reference claims that theconcentrate can be used to reduce bacterial, microbial, fungicidal orviral population on a dermal tissue of a mammal. The reference disclosesthat cationic active” is the ingredient that provides antimicrobialactivity. The reference discloses that the concentrate may contain askin conditioner such as polyethylene glycol.

Menachery et al., Pathogenic Influenza Viruses and Coronaviruses UtilizeSimilar and Contrasting Approaches To Control Interferon-Stimulated GeneResponses, American Society of Microbiology, 2014, 5(3): 1-11, disclosesthat influenza viruses and coronaviruses exhibit differences in terms ofreplication, immune stimulation, and overall lethality.

Li, Structure, Function and Evolution of Coronavirus Spike Proteins,Annu. Rev. Virul. 2016, 3(1):237-261, discusses the evolution of twocritical functions of coronavirus spike proteins, receptor recognitionand membrane fusion, in the context of the corresponding functions fromother viruses and host cells.

The cited references are incorporated by reference in their entiretyherein.

Neutrogena Corp, Los Angeles, Calif., markets and sells a Neutrogena®Ultra Gentle Daily Cleanser product that contains the use of potassiumacrylates copolymer as a viscosity increasing agent.

Johnson & Johnson Consumer Inc. markets and sells products, includingJohnson's Head to Toe Baby Wash; Johnson's Baby Moisture Wash; andJohnson's Baby Wipes that contain the use of potassium acrylatescopolymer as a viscosity increasing agent.

Hand sanitizers are generally used to decrease infectious agents on thehands. They are available as liquids, gels, and foams. Alcohol-basedversions and non-alcohol based versions are available. Alcohol-basedversions typically contain some combination of isopropyl alcohol,ethanol (ethyl alcohol), or n-propanol, with versions containing 60% to95% alcohol being the most effective. Care should be taken as they areflammable. Alcohol-based hand sanitizer works against a wide variety ofmicroorganisms. Non-alcohol based versions, which typically containbenralkonium chloride or triclosan, are less effective thanalcohol-based ones.

In 2020, BlueWillow Biologics, Inc. launched NanoBio Project nasalantiseptic solution containing OTC monograph benzalkonium chloride. Theproduct is applied by thoroughly swabbing the skin inside of eachnostril.

SUMMARY OF THE INVENTION

This invention relates to a method of inhibiting entry of envelopedviruses into cells comprising, consisting essentially of and consistingof contacting said viruses with an anti-viral composition comprising atleast one high molecular weight hydrophobically modified polymer in anamount effective to inhibit entry of these viruses into cells.Surprisingly, we have found that low concentrations of certain highmolecular weight hydrophobically modified polymers known for theirgentle properties are able successfully to inhibit entry of envelopedviruses into host cells and thus inhibit transmission of viruses to thehosts.

We believe that these polymers would not encounter or engender some ofthe historical problems with antiviral treatments, such as drugresistance, narrow breadth of neutralization and host cellular toxicity.The high molecular weight hydrophobically modified polymers useful inthe methods and compositions of this invention are broadly activeagainst several viral types and across multiple viral strains.Additionally, these polymers work through a non-specific mechanism ofentry inhibition, thereby increasing their chances for inhibitorysuccess and decreasing the likelihood of resistance. Furthermore, asthese polymers are exceptionally gentle on mucosal tissues, they havelittle or no toxicity to human tissues.

Our bodies are challenged by viruses on a daily basis and our immunesystem, including our skin barrier, is designed to minimize the numberof viruses that reach infectable surfaces. The high molecular weighthydrophobically modified polymers useful in the methods and compositionsof this invention block the ability of the virus to bind to and/or entercells, thereby reducing the probability that an infectious virus canreach a target cell and cause a systemic infection. Viral infection ispartially the result of a stochastic process—the more viruses that comein contact with infectable cells, the more likely that tissue is to beinfected—therefore, use of these polymers to block infectious virusesbenefits the immune system, further reduces chances of infection andpromotes general good health. The methods and compositions of thisinvention using high molecular weight hydrophobically modified polymersare surprisingly effective at reducing the number of infectious virionsacross a broad range of viral types and strains while remaining gentleand non-irritating to human tissues.

The disclosure may best be understood by reference to the followingdescription taken in conjunction with the accompanying figures, whichillustrate particular embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of the coronavirus structure and viralreceptor ACE2 on the host cell surface.

FIG. 2 is an illustration showing broad-spectrum activity of arbidol andits molecular mechanisms of action at the cellular level.

FIG. 3 is an illustration showing the polymers of the invention may showactivity against COVID-19 by inhibiting entry of the virus in a hostcell.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As used herein, the term “infectable surface” means a surface of aliving animal the cells of which may be infected by a virus, includingmammals such as human beings. Examples of such infectable surfaces areexternal skin tissues and mucosal tissues. Mucosal tissues include oral,ocular, nasal, vaginal and rectal tissue.

As used herein, the term “ingestible surface” refers to the surface offoods, including the surface of fruits and vegetables. As used herein,the term “hard surface” refers to surfaces found in the environment suchas tables, chairs, walls, and other inanimate surfaces with which skinand/or mucosal tissue may come into contact and on which viruses mayreside. The term “internal surface” refers to internal organ surfacesand internal tissues and fluids within the body of a living organism.

As used herein, the term “virus” means a small infectious agent that canreplicate only inside the living cells or organisms. Virus particlescontain the following parts: genetic material made from either RNA orDNA and a protein coat that protects the genetic material. In somecases, virus particles are surrounded by an envelope of lipids aroundthe protein coat when the virus particles are outside a cell. Virusparticles that contain such an envelope of lipids are referred to hereinas “enveloped viruses”. Enveloped viruses include the followingorganisms: poxviridae including, but not limited to, molloscumcontagiosum, chickenpox, smallpox and other pox viruses, Herpesviridaeincluding herpes simplex virus 1 and herpes simplex virus 2,retroviridae including Lentivirus including Human ImmunodeficiencyVirus.

As used herein, the term “surfactant” is a surface active agent, or asubstance that, when dissolved in water or an aqueous solution, reducesits surface tension or the interfacial tension between it and anotherliquid.

As used herein, the term “inhibiting transmission” means one or more ofthe following: (i) impeding the entry of a virus into a host cell; (ii)substantially stopping the introduction of a virus from one individual,infectable surface or contact surface to another; and/or (iii) reducingdamage to mucosal membranes such that the membranes retain theirintegrity and protect against infection by the virus.

As used herein, the hydrophilic-lipophilic balance (“HLB”) is a measureof the degree to which a surfactant is hydrophilic or lipophilic, asdetermined by calculating values for different regions of the surfactantmolecule in accordance with methods known to those of skill in the art.

Preferably, the method of this invention relates to a method ofinhibiting entry of enveloped viruses into cells comprising, consistingessentially of and consisting of contacting said viruses with ananti-viral composition comprising, consisting essentially of andconsisting of at least one high molecular weight hydrophobicallymodified polymer in an amount effective to inhibit entry of viruses intocells. The methods of this invention further include the application ofthe compositions set forth herein onto infectable surfaces as well asonto ingestible surfaces. The methods further include contacting viruseswith the anti-viral compositions of this invention.

The methods of this invention also include the application of thecompositions of this invention to ingestible surfaces such as food aswell as to hard surfaces into which skin and mucosal tissue might comeinto contact. As such, the presence of the compositions of thisinvention would work to inhibit entry of viruses present on ingestibleand hard surfaces into cells contained on skin and mucosa and internaltissues and fluids.

Preferably, the compositions of this invention contain at least about55% water.

The compositions of this invention may contain surfactant having aHydrophilic-Lipophilic Balance (hereinafter, “HLB”) greater than about12. Preferably, the compositions of the present invention contain lessthan about 9% by weight of surfactant having an HLB of greater thanabout 12. More preferably, the compositions of this invention shouldcontain between about 0.375% and about 9% by weight of surfactant and,most preferably, between about 0.375% and about 6%, even morepreferably, between about 0.375% and about 3% by weight of surfactanthaving an HLB of greater than about 12. Further, the HLB is preferablygreater than about 16.

Notwithstanding the foregoing, the compositions of this invention mayadditionally contain surfactants having an HLB of less than 16. Thesurfactant levels of the compositions of this invention should besufficiently low so as not to produce irritation of the skin of a mammalupon exposure or tissue disruption to the cells of the skin or mucosa ofsaid mammal. Such tissue disruption results in providing easier viralentry into the cells. Nonetheless, compositions capable of being usedfor cleansing as well as virus inhibition are desirable for applicationto living organisms, including mammals and preferably, humans.

Preferably, the compositions useful in the methods of this inventionhave a Trans-Epithelial Permeability (hereinafter, “TEP”), as describedbelow, of at least 3.7.

The compositions of this invention may be applied to infectable surfacesof a living entity including mammals, reptiles, birds, fish, bacteria,and the like. Infectable surfaces of these living entities may include,but are not limited to, skin, mucosal and internal tissues. Mucosaltissue includes, but is not limited to oral tissue, nasal tissue,vaginal tissue, rectal tissue or a combination thereof. Importantly, thecompositions and methods of this invention do not disrupt thesebiological surfaces or cause significant irritation of those surfaces.

Polymeric Material

Examples of polymeric materials useful in the compositions and methodsof this invention include high-molecular weight hydrophobically modifiedpolymer as described in U.S. Pat. No. 7,772,421. In particular, thepolymer should have the following characteristics:

-   (a) about 25 to about 70 weight percent based on total monomers of    at least one C₃-C₈ alpha beta-ethylenically unsaturated carboxylic    acid monomer of the structure (II):

RCH═C(R′)COOH   (II)

-   -   wherein R is H, CH₃, or —CH₂COOX; and wherein if R is H, then R′        is H, C₁-C₄ alkyl, or —CH₂COOX; if R is —C(O)OX, then R′ is H or        —CH₂C(O)OX; or if R is CH₃, then R′ is H; and X, if present, is        H or C₁-C₄ alkyl;

(b) about 30 to about 70 weight percent based on total monomers of atleast one copolymerizable non-ionic C₂-C₁₂ alpha beta-ethylenicallyunsaturated monomer of the structure (III):

H₂C═CYZ   (III)

-   -   wherein Y is H, CH₃, or Cl; Z is CN, Cl, —COOR′, —C₆H₄R′,        —COOR″, or —HC═CH₂; and wherein R is C₁-C₈ alkyl or C₂-C₈        hydroxy alkyl; and wherein R′ is H, Cl, Br, or C₁-C₄ alkyl; and        R″ is C₁-C₈ alkyl; and

-   (c) about 0.05 to about 20 weight percent based on total monomer    weight of at least one ethylenically unsaturated monomer represented    by the structure selected from a group consisting of structures IV,    VI and VII;    wherein structure IV represents an ester of an alkoxylated fatty    alcohol

wherein R is H or CH₃; wherein R₁ is a —(CH₂)_(p)H alkyl chain; whereinp is an integer from 1 to about 4; wherein j is an integer from 1 toabout 50; wherein k is an integer from 0 to about 20; wherein h is 1 or2; and wherein X has the following structure (V):

-   -   wherein m and n are, independently, are positive integers from 1        to 39 and m+n represents an integer from 4 to 40;    -   wherein structure VI is an ester of an alkoxylated nopol

wherein R₃ is H or CH₃; R₄ is an alkyl chain containing 1 to about 4carbons; M is an integer from 1 to about 50; and N is 0 or an integer ofless than or equal to M, and wherein said structure, VII, represents anester of an alkoxylated fatty alcohol

wherein R₁ is either H or methyl or ethyl or propyl or combination ofany of them, K is an integer from 1 to about 500, R is methyl or ethylor propyl or butyl and X is H or a moiety represented by structure V.

In a preferred embodiment of the present invention, the high-molecularweight hydrophobically modified polymer is preferably ahydrophobically-modified alkali-swellable emulsion (HASE) polymer suchas those described in EP 226097 B1, EP 705852 B1, U.S. Pat. Nos.4,384,096, and 5,874,495 and 8,211,850 B2, the disclosures of which areincorporated herein by reference. HASE polymers that we believe may beuseful in the compositions and methods of this invention include, butare not limited to the following: Acrylates/Steareth-20 MethacrylateCopolymer, Acrylates/Steareth-20 Methacrylate Crosspolymer,Acrylates/Ceteth-20 Itaconate Copolymer), Acrylates/Beheneth-25Methacrylate Copolymer (available commercially as ACULYN™ 28 from DowChemical Company of Midland, Mich.), hydrophobically modified anionicthickener (available commercially as ACRYSOL™ TT-935 from Dow ChemicalCompany of Midland, Mich.), and polyacrylate-33. Most preferably, theHASE polymer used in the compositions and methods of this invention isPolyacrylate-33, sold under the tradename of Rheomer® 33 (available fromRhodia, Cranbury, N.J.). Such high-molecular weight hydrophobicallymodified polymer, when formulated into low-to-mediumsurfactant-containing cleanser, is shown to display high thickeningefficiency and good suspension properties and shear-thinning rheology.

This polymer is formed in an emulsion polymerization with a seed step.The monomers are pre-emulsified in aqueous phase (water and surfactant)and then semi-continuously added to the polymerization reactor. Rheomer®33 is a copolymer of methacrylic acid (MAA), ethyl acrylate (EtA),Sipomer HPM300 and HPM400 in the following proportions 36.2/51.8/5/7wt %respectively. The finished product is a 30% wt. latex in water. Thepolymer is formed via the following reaction scheme:

As used herein the term “high molecular weight” polymer refers to apolymer having a number average molecular weight (M_(n)) of at leastabout 100,000 or more as measured by gel permeation chromatography (GPC)calibrated with a poly(methyl methacrylate) (PMMA) standard. In certainpreferred embodiments, high-molecular weight polymers are those havingmolecular weight ranges of from about 100,000 to about 700,000 M_(n),more preferably from about 200,000 to about 700,000 M_(n), and morepreferably between about 400,000 and 700,000 M_(n).

A “hydrophobic moiety” is hereby defined as a nonpolar moiety thatcontains at least one of the following: (a) a carbon-carbon chain of atleast four carbons in which none of the four carbons is a carbonylcarbon or has a hydrophilic moiety bonded directly to it; (b) two ormore alkyl siloxy groups (—[Si(R)₂—O]—); and/or (c) two or moreoxypropylene groups in sequence. A hydrophobic moiety may be, orinclude, linear, cyclic, aromatic, saturated or unsaturated groups. Incertain preferred embodiments, hydrophobic moieties comprise a carbonchain of at least six or more carbons, more preferably seven or morecarbons in which none of the carbons in such chain have a hydrophilicmoiety bonded directly thereto. Certain other preferred hydrophobicmoieties include moieties comprising a carbon chain of about eight ormore carbon atoms, more preferably about 10 or more carbon atoms inwhich none of the carbons in such chain have a hydrophilic moiety bondeddirectly thereto. Examples of hydrophobic functional moieties mayinclude esters, ketones, amides, carbonates, urethanes, carbamates, orxanthate functionalities, and the like, having incorporated therein orattached thereto a carbon chain of at least four carbons in which noneof the four carbons has a hydrophilic moiety bonded directly to it.Other examples of hydrophobic moieties include groups such aspoly(oxypropylene), poly(oxybutylene), poly(dimethylsiloxane),fluorinated hydrocarbon groups containing a carbon chain of at leastfour carbons in which none of the four carbons has a hydrophilic moietybonded directly to it, and the like.

As used herein, the term “hydrophilic moiety,” is any anionic, cationic,zwitterionic, or nonionic group that is polar. Nonlimiting examplesinclude anionics such as sulfate, sulfonate, carboxylicacid/carboxylate, phosphate, phosphonates, and the like; cationics suchas: amino, ammonium, including mono-, di-, and trialkylammonium species,pyridinium, imidazolinium, amidinium, poly(ethyleneiminium), and thelike; zwitterionics such as ammonioalkylsulfonate,ammonioalkylcarboxylate, amphoacetate, and the like; and nonionics suchas hydroxyl, sulfonyl, ethyleneoxy, amido, ureido, amine oxide, and thelike.

As used herein, the term “hydrophobically-modified material” refersgenerally to any material having one or more hydrophobic moietiesattached thereto or incorporated therein. Certain preferredhydrophobically-modified materials include materials having a hydrophobecomprising six carbons (C₆) or more, preferably eight carbons (C₈) ormore, more preferably from 10 to 16 carbons (C₁₀₋₁₆). Examples ofcertain types of preferred hydrophobically-modified materials includehydrophobically-modified polymers. Such polymers may be formed, forexample, by polymerizing one or more hydrophobic monomers and,optionally, one or more co-monomers, to form a polymer havinghydrophobic moieties incorporated therein, and/or also by reactingpolymer materials with compounds comprising hydrophobic moieties toattach such compounds to the polymers. The high molecular weighthydrophobically modified polymers useful in the compositions and methodsof this invention are preferably present in said compositions in amountsthat are effective to inhibit substantially the entry of envelopedviruses into cells and/or to inhibit virus transmission to cells.Accordingly, the compositions and methods of this invention inhibitvirus entry into said cells and results in the reduction of thepotential for viral infection. Preferably, they should be present in thecompositions of this invention in an amount of from about 0.00005% toabout 3% percent by weight of the composition. More preferably, the highmolecular weight hydrophobically modified polymers are present in anamount of from about 0.00005% to about 0.5 percent by weight of thecomposition. Most preferably, the high molecular weight hydrophobicallymodified polymers are present in an amount of from about 0.00005% toabout 0.01% percent by weight of the composition.

The compositions of this invention may be in the form of a lotion orliquid capable of being applied on the surface of the skin or on aninanimate surface that can contain viruses or bacteria. It may also be acomposition which is applied to a mucosal surface such as the surfacesof the nasal cavity or vaginal cavity and can be used as a vaginalmicrobicide. These types of composition may be more viscous and may bebased on a gel formation. The compositions of this invention may becoated onto an absorbent article such as a vaginal or nasal tampon forplacement in contact with mucosal surfaces to inhibit viruses in suchbiologic environments. The compositions of this invention may also beformulated in such a delivery form that they may be injected into thebody at appropriate sites where viruses may reside on internal surfaces.

The compositions of this invention may be made into a wide variety ofproduct types that include but are not limited to liquids, lotions,creams, gels, sticks, sprays, shaving creams, ointments, cleansingliquid washes and solid bars, shampoos, pastes, powders, mousses, wipes,patches, wound dressing and adhesive bandages, hydrogels and films.These product types may contain several types of cosmetically acceptabletopical carriers including, but not limited to solutions, emulsions(e.g., microemulsions and nanoemulsions), gels, solids and liposomes.The following are non-limiting examples of such carriers. Other carriersmay be formulated by those skilled in the art of formulating suchproduct types.

Preferred compositions of the invention include polymer containing gels;polymer containing drops, including, e.g., eye drops; polymer containingcontact lens solutions; polymer containing sprays, e.g., face/bodysprays, nasal sprays, and mouth and throat sprays; and polymercontaining inhalants.

The compositions of the invention may also be used as a coating on or inpersonal protective equipment. Personal protective equipment, which iscommonly referred to as

“PPE”, is any equipment worn to minimize exposure to a variety ofhazards. Examples of PPE include full body suits, gloves, gowns, masks,respirators and eye and foot protection.

The topical compositions useful in the methods of this invention may beformulated as solutions. Solutions preferably contain an aqueous solvent(e.g., from about 50% to about 99.99% or from about 90% to about 99% ofa cosmetically acceptable aqueous solvent).

Topical compositions useful in the methods of this invention may beformulated as a solution containing an emollient. Such compositionspreferably contain from about 2% to about 50% of an emollient(s). Asused herein, “emollients” refer to materials used for the prevention orrelief of dryness, as well as for the protection of the skin. A widevariety of suitable emollients is known and may be used herein. Sagarin,Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972)and the International Cosmetic Ingredient Dictionary and Handbook, eds.Wenninger and McEwen, pp. 1656-61, 1626, and 1654-55 (The Cosmetic,Toiletry, and Fragrance Assoc., Washington, D.C., 7^(th) Edition, 1997)(hereinafter “ICI Handbook”) contain numerous examples of materials foruse in the compositions and methods of this invention.

A lotion may also be made from such a solution. Lotions preferablycontain from about 1% to about 20% (more preferably, from about 5% toabout 10%) of an emollient(s) and from about 50% to about 90% (morepreferably, from about 60% to about 80%) of water.

Another type of product that may be formulated from a solution is acream. A cream preferably contains from about 5% to about 50% (morepreferably, from about 10% to about 20%) of an emollient(s) and fromabout 45% to about 85% (more preferably from about 50% to about 75%) ofwater.

Yet another type of product that may be formulated from a solution is anointment. An ointment may contain a simple base of animal or vegetableoils or semi-solid hydrocarbons. An ointment may preferably contain fromabout 2% to about 10% of an emollient(s) plus from about 0.1% to about2% of a thickening agent(s). A more complete disclosure of thickeningagents or viscosity increasing agents useful herein may be found inSagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp.72-73 (1972) and the ICI Handbook pp. 1693-1697.

The topical compositions useful in the methods of this invention mayalso be formulated as emulsions. If the carrier is an emulsion,preferably from about 1% to about 10% (e.g., from about 2% to about 5%)of the carrier contains an emulsifier(s). Emulsifiers may be nonionic,anionic or cationic. Suitable emulsifiers are set forth in, for example,U.S. Pat. Nos. 3,755,560, 4,421,769, McCutcheon's Detergents andEmulsifiers, North American Edition, pp. 317-324 (1986), and the ICIHandbook, pp.1673-1686, which are incorporated herein by reference.

Lotions and creams may also be formulated as emulsions. Preferably suchlotions contain from 0.5% to about 5% of an emulsifier(s). Such creamswould preferably contain from about 1% to about 20% (more preferably,from about 5% to about 10%) of an emollient(s); from about 20% to about80% (more preferably, from 30% to about 70%) of water; and from about 1%to about 10% (more preferably, from about 2% to about 5%) of anemulsifier(s).

Other compositions useful in the methods of this invention include gelsand liquid compositions that may be applicable to mucosal surfaces forinhibiting viral transmission.

Mucosal surfaces include but are not limited to the vagina, rectum,nasal passages, mouth and throat. Preferably, such compositions shouldinclude at least one polyhydric alcohol, including glycerin,polyethylene glycol, propylene glycol, sorbitol or a combinationthereof. Other polyhydric alcohols know to those of ordinary skill inthe art may be used in the compositions and methods of this invention,including polyethylene glycols ranging from molecular weight of fromabout 300 to about 1450. Preferably, there should be from about 0.1 toabout 50% by weight of glycerin and from about 2 to about 40% by weightof propylene glycol.

The mucosal compositions of this invention should also contain one ormore water-soluble cellulose-derived polymers. Preferably, such polymersshould be a cellulose gum such as one or more hydroxyalkylcellulosepolymer. More preferably, the hydroxyalkylcellulose polymer should beone or more of hydroxyethylcellulose, hydroxymethylcellulose,hydroxypropylcellulose, hydroxypropylmethylcellulose and the like.Preferably, the cellulose-derived polymer should be present in thecompositions of this invention in the amount of from about 0.1 to about2% by weight of the composition.

The compositions of this invention intended for vaginal use may alsocontain one or more spermicides including but not limited to nonoxynol-9and the like. Although such spermicides may be classified assurfactants, they generally have an HLB of less than 16 and are notuseful as or in cleansing compositions and do not foam.

Preferably, an inorganic base may be used to adjust the pH of thecomposition to be compatible with the vaginal, oral or rectal mucosa.Potassium hydroxide or another alkali metal or alkaline earth metal basemay be useful to provide the appropriate pH. Of course, any otherphysiological acceptable base may also be used in this manner. Fromabout 0.05 to about 5% by weight inorganic base is preferably used.

The compositions of this invention may be prepared in accordance withthose methods and processes known to those of skill in the art, or inaccordance with the methods of preparation of this invention. Forexample, water-soluble components such as glycerin, propylene glycol,sorbitol, inorganic base, preservatives, and the like may be dissolvedin water and to that combination cellulose-derived polymers may beadded. Another method of preparation is mixing all the ingredients intoa slurry without water, and then adding the slurry to water.

The composition is preferably substantially free of surfactant,including anionic, cationic, amphoteric, or nonionic surfactants.

Included in a liquid or lotion formation of the composition may bewater, oils, preservatives, emulsifiers, viscosity enhancers,emollients, electrolytes, fragrance, buffers, pH modifiers, skinprotectants, metal ion sequestrants and the like.

The compositions of this invention may be useful in formulating handand/or body washes, fruit and/or vegetable washes, ingestiblecompositions, suppositories, nasal sprays, post-surgical tampons and thelike, which may be applied to surfaces or placed in the body to inhibittransmission of viruses. The compositions of this invention may becoated onto an absorbent article such as a vaginal or nasal tampon forplacement in contact with mucosal surfaces to inhibit viruses in suchbiologic environments.

Methods

There are various testing methods that have been employed herein toevaluate different aspects of the methods and compositions of thisinvention and their effects upon skin, mucosa and viruses when exposedto the compositions of the invention. The Trans-Epithelial Permeability(“TEP”) test is used in the instant methods and in the followingExamples. The TEP test is used to determine the degree to which acomposition causes irritation to the skin or mucosa.

Trans-Epithelial Permeability Test (“TEP Test”):

Irritation to the eyes and/or skin expected for a given formulation ismeasured in accordance with the Invittox Protocol Number 86 (May 1994),the “Trans-epithelial Permeability (TEP) Assay” and set forth in U.S.Pat. No. 7,157,414, which are incorporated herein by reference. Ingeneral, the ocular and/or skin irritation potential of a product may beevaluated by determining its effect on the permeability of a cell layer,as assessed by the leakage of fluorescein through the layer. Monolayersof Madin-Darby canine kidney (MDCK) cells are grown to confluence onmicroporous inserts in a 24-well plate containing medium or assay bufferin the lower wells. The irritation potential of a product is evaluatedby measuring the damage to the permeability barrier in the cellmonolayer following a 15 minute exposure to dilutions of the product.Barrier damage is assessed by the amount of sodium fluorescein thatleaks through to the lower well after 30 minutes, as determinedspectrophotometrically. The fluorescein leakage is plotted against theconcentration of test material to determine the EC₅₀ (the concentrationof test material that causes 50% of maximum dye leakage, i. e., 50%damage to the permeability barrier). Higher scores are indicative ofmilder formulas.

Exposure of a layer of MDCK cells grown on a microporous membrane to atest sample is a model for the first event that occurs when an irritantcomes in contact with the eye. In vivo, the outermost layers of thecorneal epithelium form a selectively permeable barrier due to thepresence of tight junctions between cells. On exposure to an irritant,the tight junctions separate, thereby removing the permeability barrier.Fluid is imbibed to the underlying layers of epithelium and to thestroma; causing the collagen lamellae to separate, resulting in opacity.The TEP assay measures the effect of an irritant on the breakdown oftight junctions between cells in a layer of MDCK cells grown on amicroporous insert. Damage is evaluated spectrophotometrically, bymeasuring the amount of marker dye (sodium fluorescein) that leaksthrough the cell layer and microporous membrane to the lower well.

Evaluation of Activity Against HIV-1_(IIIB) in CEM-SS Cells

Fifty microliters (50 μL) of CEM-SS cells at a density of 2.5×10³cells/well in 10% complete Roswell Park Memorial Institute Medium(“RPMI”)-1640 (10% FBS with 1% L-glutamine and 1%Penicillin/Streptomycin, available commercially from Invitrogen locatedin Carlsbad, California) media are plated in a 96-well round bottomplate. One-hundred microliters (100 μL) of each polymer at 6concentrations are added in triplicate followed by 50 μL of HIV-1_(IIIB)at a pre-determined titer. The cultures are incubated for 6 days at 37°C./5% CO₂. Following the incubation, the cells are stained with XTT forevaluation of compound efficacy and cellular toxicity, as describedbelow. AZT is evaluated in parallel as an assay positive controlcompound.

XTT Staining for Cell Viability and Compound Cytotoxicity:

TC₅₀ values for the test materials are derived by measuring thereduction of the tetrazolium dye XTT(2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide). XTT in metabolically activecells is metabolized by the mitochondrial enzyme Nicotinamide adeninedinucleotide phosphate oxidase (“NADPH”) to a soluble formazan product.XTT solution is prepared daily as a stock of 1 mg/ml in RPMI-1640without additives. Phenazine methosulfate (PMS) solution is prepared at0.15 mg/ml in DPBS and stored in the dark at −20° C. XTT/PMS stock isprepared immediately before use by adding 40 μL of PMS per ml of XTTsolution. Fifty μL (50 μL) of XTT/PMS is added to each well of the plateand the plate incubated for 4 hours at 37° C. The 4 hour incubation hasbeen empirically determined to be within the linear response range forXTT dye reduction with the indicated numbers of cells for each assay.The plates are sealed and inverted several times to mix the solubleformazan product and the plate is read at 450 nm (650 nm referencewavelength) with a Molecular Devices SpectraMax Plus 384 96 well plateformat spectrophotometer.

Materials:

A high molecular weight hydrophobically modified alkali swellableemulsion (HASE) polymer, Polyacrylate-33 (available as Rheomer® 33 fromRhodia, Cranbury, N.J.) was used in the compositions of this inventionas the high molecular weight hydrophobically modified polymer.

EXAMPLE 1 Inventive Examples E1-E5 and Comparative Examples C1-C3:Preparation of Compositions to be Tested

Inventive examples E1-E5, and Comparative examples C1-C3 were preparedaccording to the descriptions set forth below with materials in theamounts listed in Table 1.

TABLE 1 Each of the compositions of Table 1 was independently preparedas follows: Ingredient E1 E2 E3 E4 E5 C1 C2 C3 INCI name w/w % w/w % w/w% w/w % w/w % w/w % w/w % w/w % Polyacrylate-33 0.75 3.0 0.0375 0.180.09 9.90 Lauryl Glucoside 0.375 9.0 0.375 9.0 9.0 (unpreserved)Ammonium 14.5 14.5 Laureth Sulfate Cocamide MEA 2.1 2.1 Ammonium Xylene0.8 0.8 Sulfonate Acrylates/C10-C30 0.3 alkyl acrylate cross-polymerDMDM Hydantoin 0.4 0.4 C1 90.10 Sodium Hydroxide Qs qs qs qs Water Qs qsqs qs qs E1-2.67 gms of Polyacrylate-33 (28% activity) was added to96.62 gms of deionized water and stirred on a mixing plate, heating to65° C. until Polyacrylate-33 was completely mixed and uniform. 0.71 gmsof Lauryl Glucoside (52.5% activity) was added to the mixture at 40° C.and mixed until uniform. pH was adjusted to 6.55 using 20% sodiumhydroxide solution. E2-10.71 gms of Polyacrylate-33 (28% activity) wasadded to 71.88 gms of deionized water and stirred on a mixing plate,heating to 65° C. until Polyacrylate-33 was completely mixed anduniform. 17.41 gms of Lauryl Glucoside (52.5% activity) was added to themixture at 40° C. and mixed until uniform. pH was adjusted to 6.53 using20% sodium hydroxide solution. E3 - 0.14 gms of Polyacrylate-33 (28%activity) was added to 99.15 gms of deionized water and stirred on amixing plate, heating to 65° C. until Polyacrylate -33 was completelymixed and uniform. 0.71 gms of Lauryl Glucoside (52.5% activity) wasadded to the mixture at 40° C. and mixed until uniform. pH was measuredat 6.62 E4-0.64 gms of Polyacrylate-33 (28% activity) was added to 82.22gms deionized water and stirred on a mixing plate, heating to 65° untilPolyacrylate -33 was completely mixed and uniform. 17.14 gms of LaurylGlucoside (52.5% activity) was added to the mixture at 40° C. and mixeduntil uniform. pH was adjusted to 6.53 using 20% citric acid solution.E5-0.32 gms of Polyacrylate-33 (28% activity) was added to 82.54 gms ofdeionized water and stirred on a mixing plate, heating to 65° C. untilPolyacrylate-33 was completely mixed and uniform. 17.14 gms of LaurylGlucoside (52.5% activity) was added to the mixture at 40° C. and mixeduntil uniform. pH was adjusted to 6.50 using 20% citric acid solution.C1-14.5 gms of Ammonium Laureth Sulfate was added to 82.2 gms ofdeionized water and heated to 55-60° C. with continuous mixing. 0.8 gmsof Ammonium Xylene Sulfonate and 2.1 gms of Cocamide MEA were added tothe mixture one after the other with continuous mixing uniform. Themixture was allowed to cool and 0.4 gms of DMDM Hydantoin was added tothe mixture at 40° C. pH was adjusted to 6.43 using 20% citric acidsolution. C2-0.3 gms of Acrylates/C10-C30 alkyl acrylate cross-polymerwas added to 81.9 gms of deionized water with continuous mixing andheating to 55-60° C. 14.5 gms of Ammonium Laureth Sulfate, 0.8 gms ofAmmonium Xylene Sulfonate and 2.1 gms of Cocamide MEA were then added tothe mixture, one after the other with continuous mixing until uniform.The mixture was allowed to cool and 0.4 gms of DMDM Hydantoin was addedto the mixture at 40° C. pH was adjusted to 6.49 using 20% sodiumhydroxide solution. C3-9.9 gms of Polyacrylate-33 was added to 90.1 gmsof C1 and mixed until uniform with slight heating to 50-60° C. pH wasadjusted to 6.41 using 20% sodium hydroxide solution.

EXAMPLE 2 Mildness Testing via Trans Epithelium Permeation (TEP) Test

Inventive examples E1-E5 and comparative examples C1-C3 were tested forTEP as per the method detailed set forth above, TEP scores shown inTable 3A and Table3B.

TABLE 3A Sample TEP: EC₅₀ E1 37.06 +/− 2.41  E2 4.83 +/− 0.17 E3 35.70+/− 8.13  E4 3.68 +/− 0.21 E5 3.78 +/− 0.36

TABLE 3B Sample *TEP: EC₅₀ C1 0.92 +/− 1.27 C2 0.94 +/− 0.96 C3 1.16 +/−1.01 *Average of 2 replicates

As shown in tables 3A and 3B, inventive examples E1-E5 demonstratedsuperior mildness in TEP assay whereas comparative examples C1-C3 showedpotential for membrane-damage that may result in penetration of agentsvia mucosal tissues.

EXAMPLE 4

Activity of Embodiment E1 against HIV-1

Following the protocol described above, embodiment E1 was tested againstHIV-1 (Table 4).

TABLE 4 E1 EC50 Virus Strain Tropism/Subtype (μg/ml) HIV-1 IIIB CXCR4/B6.0

As shown in Table 4, inventive example E1 exhibits activity atconcentrations from about 6 ug/mL against HIV-1.

What is claimed is:
 1. A method of inhibiting entry of enveloped virusesinto cells comprising contacting said viruses with an anti-viralcomposition comprising at least one high molecular weighthydrophobically modified polymer in an amount effective to inhibit entryof viruses into cells, wherein said anti-viral composition comprisesless than about 9% by weight of surfactant having an HLB greater thanabout
 12. 2. A method according to claim 1 wherein said compositioncomprises between about 0.375% and 9% by weight of surfactant.
 3. Amethod according to claim 2 wherein said composition comprises betweenabout 0.375% and 6% by weight of surfactant.
 4. A method according toclaim 2 wherein said composition comprises between about 0.375% and 3%by weight of surfactant.
 5. A method according to claim 1 wherein theTEP of said anti-viral composition is greater than about 3.7.
 6. Amethod according to claim 1 further comprising applying said anti-viralcomposition to infectable surfaces of a subject.
 7. A method accordingto claim 6 wherein said infectable surfaces comprise one or more of thegroup consisting of skin and mucosal tissue of a subject.
 8. A methodaccording to claim 7 wherein said mucosal tissue comprises tissueselected from the group consisting of oral tissue, ocular tissue, nasaltissue, vaginal tissue, or rectal tissue and a combination thereof.
 9. Amethod according to claim 1 wherein said the number average molecularweight (M_(n)) of said high molecular weight hydrophobically modifiedpolymer is at least about 100,000 or more as measured by gel permeationchromatography (GPC) calibrated with a poly(methyl methacrylate) (PMMA)standard.
 10. A method according to claim 1 wherein said high molecularweight hydrophobically modified polymer is a hydrophobicafly modifiedalkali swellable emulsion polymer selected from the group consisting ofAcrylates/Steareth-20 Methacrylate Copolymer, Acrylates/Steareth-20Methacrylate Crosspolymer, Acrylates/Ceteth-20 Itaconate Copolymer),Acrylates/Beheneth-25 Methacrylate Copolymer, hydrophobically modifiedanionic thickener and polyacrylate-33 and a combination thereof.
 11. Amethod according to claim 7 wherein said high molecular weighthydrophobically modified polymer comprises polyacrylate-33.
 12. A methodaccording to claim 1 wherein said high molecular weight hydrophobicallymodified polymer is present in said composition in an amount of fromabout 0.00005% to about 3% percent by weight of the composition.
 13. Amethod according to claim 1 wherein said composition further comprisesat least 55% of water.
 14. A method according to claim 13 wherein saidcomposition comprises at least 97% of water.
 15. A method according toclaim 1 wherein said viruses are selected from the group consisting ofpoxviridae, herpesviridae, retroviridae Lentivirus and a combinationthereof.
 16. A method according to claim 1 wherein said virus selectedfrom the family of herpesviridae is herpes simplex virus 1, herpessimplex virus 2 and a combination thereof.
 17. A method according toclaim 16 wherein said virus selected from the family retroviridaeLentivirus is Human Immunodeficiency Virus Type
 1. 18. A methodaccording to claim 1 wherein said inhibition of virus entry into saidcells results in the reduction of potential for viral infection.
 19. Amethod according to claim 1 wherein the anti-viral composition does notsubstantially disrupt biological surfaces.
 20. A method of inhibitingentry of enveloped viruses comprising contacting infectable surfaceswith an anti-viral composition comprising at least one high molecularweight hydrophobically modified polymers in an amount effective toinhibit entry of viruses into cells, said anti-viral compositioncomprises less than about 9% by weight of surfactant having an HLBgreater than about
 12. 21. A method of inhibiting entry of envelopedviruses according to claim 21 further comprising contacting said viruseswith said anti-viral composition.
 22. An anti-viral compositioncomprising at least one high molecular weight hydrophobically modifiedpolymers in an amount effective to inhibit entry of viruses into cellsand at least 55% water, wherein said anti-viral composition comprisesless than about 9% by weight of surfactant having an HLB greater thanabout
 12. 23. An anti-viral composition comprising at least one highmolecular weight hydrophobically modified polymers in an amounteffective to inhibit entry of viruses into cells and at least 97% water,wherein said anti-viral composition comprises less than about 9% byweight of surfactant having an HLB greater than about
 12. 24. A methodof inhibiting the transmission of viruses comprising applying tonon-biological surfaces a composition comprising at least one highmolecular weight hydrophobically modified polymer in an amount effectiveto inhibit entry of viruses into cells wherein said anti-viralcomposition comprises less than about 9% by weight of surfactant havingan HLB greater than
 12. 25. A method of inhibiting the transmission ofviruses comprising applying to ingestable surfaces a compositioncomprising at least one high molecular weight hydrophobically modifiedpolymers in an amount effective to inhibit entry of viruses into cellswherein said anti-viral composition comprises less than about 9% byweight of surfactant having an HLB greater than
 12. 26. A compositionaccording to claim 1 wherein said composition comprises a dosage formselected from the group consisting of: a liquid, a lotion, a cream, agel, a stick, a spray, a shaving cream, an ointment, a cleansing liquidwash, a solid bar, a shampoo, a paste, a powder, a mousse, a wipe, apatch, a wound dressing, an adhesive bandage, a hydrogel and a film. 27.A composition according to claim 9 wherein the number average molecularweight (M_(n)) of said high molecular weight hydrophobically modifiedpolymer is at least about 100,000 or more as measured by gel permeationchromatography (GPC) calibrated with a poly(methyl methacrylate) (PMMA)standard.
 28. A composition according to claim 28 wherein saidhydrophobically modified high molecular weight polymer is ahydrophobically-modified alkali swellable emulsion polymer.
 29. Acomposition according to claim 29 wherein said hydrophobically modifiedhigh molecular weight polymer comprises a hydrophobically modifiedalkali swellable emulsion polymer selected from the group consisting of:Acrylates/Steareth-20 Methacrylate Copolymer, Acrylates/Steareth-20Methacrylate Crosspolymer, Acrylates/Ceteth-20 Itaconate Copolymer),hydrophobically modified anionic thickener and polyacrylate-33 and acombination thereof and a combination thereof.
 30. A compositionaccording to claim 30 wherein said hydrophobically modified highmolecular weight polymer is polyacrylate-33.
 31. A composition accordingto claim 1 wherein said composition further comprises nonoxynol-9.